Review
Parvovirus B19 during pregnancy: a review
Elsa Giorgio1
Maria Antonietta De Oronzo2
Irene Iozza3
Angela Di Natale1
Stefano Cianci3
Giovanna Garofalo3
Anna Maria Giacobbe1
Salvatore Politi3
1
Policlinico Universitario “G. Martino”, Department of
Obstetrics and Gynecology, University of Messina, Italy
2
Department of Gynecology, University “Campus Bio-
medico”, Rome, Italy
3
Santo Bambino Hospital, Department of Microbiologi-
cal and Gynecological Sciences, University of Catania,
Italy
Corresponding author:
Elsa Giorgio
Policlinico Universitario “G. Martino”, Department of Ob-
stetrics and Gynecology, University of Messina
email address: elsagiorgio@virgilio.it
Summary
Several infections in adults warrant special consid-
eration in pregnant women given the potential fetal
consequences. Among these is parvovirus B19 de-
serves special attention since the harmful effects on
the pregnant woman and fetus. It can then cause fe-
tal anemia, non-immune fetal hydrops and fetal
death. Among cases with fetal demise, B19 is found
in significant numbers, especially in the second and
third trimesters of pregnancy. There is no specific
treatment or prophylaxis available against B19 in-
fection, but counseling of non-immune mothers and
active monitoring of confirmed maternal infections
with intervention to correct fetal anemia is likely to
decrease mortality.
Key Words: Parvovirus B19, fetal, infection, hydrops, anemia
Introduction
Parvovirus B19 is a widespread infection that may af-
fects 1-5% of pregnant women, mainly with normal preg-
nancy outcome (1,2). The prevalence of infection is
higher during epidemics - between 3 and 20% with sero-
conversion rate of 3-34% (3,4). Infection during preg-
nancy can cause a variety of other signs of fetal dam-
age. The risk of adverse fetal outcome is increased if
Journal of Prenatal Medicine 2010; 4 (4): 63-66
maternal infection occurs during the first two trimesters
of pregnancy but may also happen during the third
trimester. It is a significant cause of fetal loss throughout
pregnancy, but has a higher impact in the second half of
pregnancy when spontaneous fetal loss from other
causes is relatively rare. Parvovirus infection can cause
severe fetal anemia as a result of fetal erythroid progen-
itor cells infection with shortened half life of erythrocytes,
causing high output cardiac failure and therefore nonim-
mune hydrops fetalis (NIHF). The P antigen expressed
on fetal cardiac myocytes enables the Parvovirus B19 to
infect myocardial cells and produce myocarditis that ag-
gravates the cardiac failure. Although there are several
reports of major congenital anomalies among offspring
of mothers infected by Parvovirus, the virus does not
seem to be a significant teratogen. Since Parvovirus
B19 infection can cause severe morbidity and mortality,
it should be part of the routine work up of complicated
pregnancies. Risk assessment for maternal infection
during pregnancy is especially important during epi-
demics when sero-conversion rates are high (4).
Infection with parvovirus B19 is associated with a wide
range of clinical presentations and outcomes. Effects
may range from an uncomplicated pregnancy to severe
hydrops fetalis or intrauterine foetal death. Maternal
symptoms may be aspecific and may delay early diag-
nosis (5).
1. Spontaneous abortion
The spontaneous loss rate of fetuses affected with par-
vovirus B19 before 20 weeks’ gestation is 14.8% and af-
ter 20 weeks’ gestation is 2.3% (6,7-9). The reason is
uncertain but may be related to multisystem organ dam-
age (10).
2. Congenital anomalies
Though there have been case reports of central nervous
system (10,11), craniofacial (10,11) and eye anomalies
(10,11). In other species with other strains of parvovirus
infection, congenital anomalies have been reported
(10,11). However, is not demonstrated an association be-
tween parvovirus infection in pregnancy and increased
risk of congenital anomalies in human fetus (10,11).
3. Hydrops
Association between parvovirus infection in pregnancy
and hydrops fetalis has been clearly demostred (6-8, 12-
16). Possible mechanisms are fetal anemia (due to the
virus crossing the placenta) combined with the shorter
half life of fetal red blood cells, leading to the severe
anemia, hypoxia and high output cardiac failure. Other
possible causes are fetal viral myocarditis leading to
cardiac failure, and impaired hepatic function caused by
direct damage of hepatocytes and indirect damage due
to hemosiderin deposits (6-8, 12-15). When the infection
63
E. Giorgio et al.
was acquired before 19 to 20 weeks’ gestation (14.8%)
(6-8,16), there is a higher fetal loss rate compared to
that after 20 weeks (2.3%) (6-8,16). The ultrasound si-
gns in a fetus with hydrops, include ascites, skin ede-
ma, pleural and pericardial effusions and placental ede-
ma (10).
Diagnosis of fetal anemia
Middle cerebral artery peak systolic velocity in high-risk
pregnancies and in presence of some fetal pathology is
a very important marker of fetal anemia (17).
Middle cerebral artery peak systolic velocity (MCA-PSV)
is a high sensitive non-invasive means for determining
the degree of fetal anemia; use of MCA-PSV into man-
agement of pregnancies at risk for fetal anemia enable
to reduce the number of invasive procedures. This pa-
rameter should not yet be considered the global stan-
dard of care for diagnosis of fetal anemia because incor-
rect use by an unexperienced operator may cause more
harm than good. However, if there is a reasonably close
medical center with sonographers tranined to assess
the MCA-PSV, patients at risk for fetal anemia should be
reffered to this center (18). There is an inverse correla-
tion between MCA PSV measurements and hemoglobin
values in fetuses at risk for anemia due to maternal
blood group alloimmunization and fetal parvovirus B19
infection. The MCA PSV is a reliable method for the pre-
diction of severity of anemia in fetuses before the first in-
trauterine transfusion and in those which have under-
gone one or more transfusions, with good sensitivity and
specificity in both groups of fetuses at ris (19).
Long-term neonatal outcome
There have been few studies of the long-term effects on
children of maternal parvovirus B19 infection (7,9,16,20-
27). The neonatal complications of maternal parvovirus
B19 infection have been reported, including hepatic in-
sufficiency (9,24,25), myocarditis (20,22,26), transfusion
dependent anemia (10,11), and central nervous system
abnormalities (20,9,25). However, incidence of congen-
ital anomalies, overall learning disabilities, or neurologic
handicaps16. Through a questionnaire survey, Miller et
al.7 found no increased risk of adverse outcome in chil-
dren of mothers with parvovirus infection in pregnancy
at one year (182 children) and 7 to 10 years (129 chil-
dren) of age. Most children born to mothers who devel-
op parvovirus B19 infection in pregnancy do not appear
to suffer long-term sequelae, but further studies are
needed (21). Parvovirus B19 itself does not seem to
cause long-term neurologic morbidity, but severe ane-
mia may be an independent risk factor for long-term
neurologic sequelae (27).
Exposure/infection in pregnancy
The first thing to do for management of Parvovirus B19
is the study of parvovirus B19-specific IgG and IgM. A
pregnant woman what is exposed to or develops signs
or symptoms of parvovirus B19 infection should perform
both parvovirus B19-specific IgG and IgM., one should
64
determine if she is immune (see figure) (21,28). Par-
vovirus B19 IgM usually appears within 2 to 3 days of
acute infection and may persist up to 6 months. Par-
vovirus B19 IgG appears a few days after IgM appears
and usually remains present for life (21).
1. IgG+ IgM-
If a pregnant woman has presence of B19-specific IgG
and absence of parvovirus B19-specific IgM she can be
considered immune. It will most likely contracted the in-
fection about six months before. If the woman is immune,
she can be reassured because she will not have adverse
consequences in the pregnancy because only the pri-
mary infection in pregnancy may cause fetal harm (21).
2. IgG- IgM+
The presence of parvovirus B19 IgM antibodies with the
absence of parvovirus B19 IgG antibodies suggests ei-
ther a very recent infection or a false positive result. In
this situation, the pregnant woman must repeat the dose
parvovirus B19 IgG and IgM in 1 to 2 weeks. If the IgG
is positive, it suggests a recent infection. If both par-
vovirus B19 IgG and IgM are negative, the woman is not
immune so she is therefore susceptible to infection (21).
If she has had a recent exposure to the virus, and may
be incubating the infection, it is suggested that the IgG
and IgM tests be repeated 2 to 4 weeks later. If expo-
sure is ongoing, one may wish to repeat serology every
2 to 4 weeks. If testing reveals both parvovirus B19 IgG
and IgM to be present, this may suggest recent infection
(21). If stored blood is available from the woman, testing
may confirm seroconversion. If stored blood is not avail-
able, repeat blood work should reveal an increasing par-
vovirus B19 IgG titre if recent infection has occurred. If
the titre is not increasing, this may represent an older in-
fection (up to 6 months prior). Serologic diagnosis with
parvovirus B19 IgM alone for recent infection may be
difficult due to lab sensitivity for IgM being positive up to
6 months after acute infection. Women who is not im-
mune need to be assessed with regard to their exposure
risk so she should perform these measure: hand wash-
ing, infact this measure decreases infection (12). During
an outbreak, parents of preschool and school children
as well as employees should be informed of the risk of
infection and its management. Each woman should be
counseled about her individual risk, based on her risk of
infection, gestational age, and other obstetrical consid-
erations. The decision to leave work to try to minimize
the risk of infection during an outbreak of parvovirus B19
infection should be made by the woman after discussion
with her physician, family members, public health offi-
cials, and employers, taking into account her specific
risk. As there is no evidence that susceptible women re-
duce their risk of infection by leaving work, and one
study demonstrated no difference in infection rates be-
tween susceptible pregnant school teachers who left the
workplace and those who stayed (29), it is not recom-
mended that policies be pursued to routinely send home
women susceptible to infection (12).
If the woman has developed a recent infection, the virus
may be transmitted to the fetus and may cause nonim-
mune hydrops. Therefore, it is recommended that these
women be referred to an obstetrician or maternal-fetal
medicine specialist and that these women have serial
Journal of Prenatal Medicine 2010; 4 (4): 63-66
Parvovirus B19 during pregnancy: a review
ultrasounds to detect evidence of hydrops for 8 to 12
weeks after infection, as the development of hydrops
may be delayed (7,11,21,29,30). There are no random-
ized trials of the frequency of ultrasounds required;
however, most maternal-fetal medicine specialists per-
form ultrasonographic assessment weekly or every 2
weeks (30).
These follow-up ultrasounds could be limited to assess-
ment of amniotic fluid volume and evidence of hydrops
(level II ultrasound with documentation). As fetuses with
hydrops tend to move less, women should also be in-
structed to monitor fetal movement daily (21). If there is
a delay in establishing the woman’s immunity status,
one may wish to obtain serial ultrasounds for the detec-
tion of hydrops, until this information regarding immuni-
ty is available (31).
Diagnosis of fetal infections
Parvovirus B19 cannot usually be cultured in regular cul-
ture media. It can be identified histologically by charac-
teristic intranuclear inclusions or by the presence of viral
particles by electron microscopy (10). Viral DNA may al-
so be identified by polymerase chain reaction (PCR) of
amniotic fluid or fetal blood by cordocentesis. The most
reliable way to diagnose acute fetal infection is to detect
in amniotic fluid or fetal serum viral DNA by PCR or viral
particles by electron microscopy. Clinical use of these
tests remains to be evaluated. Although there is the pos-
sibility of diagnosing parvovirus B19 infection through
PCR on amniotic fluid obtained by amniocentesis, inva-
sive diagnosis of this condition is not required for all sus-
pected or confirmed maternal infections. If amniocente-
sis is performed for a fetal indication, a PCR for par-
vovirus B19 can be requested as part of the workup.
The presence of viral particles, however, can only be
seen during the viremic stage. The presence of par-
vovirus B19 IgM in fetal blood cannot be depended up-
on to make the diagnosis of fetal infection (32), as the
fetus does not begin to make its own IgM until 22 weeks’
gestation. There have been false negative results even
when the fetus is beyond 22 weeks (33). Elevated ma-
ternal serum alpha fetoprotein (MSAFP) levels have
been associated with fetal parvovirus B19 infection in
several case reports (34,35); but one study found the
association between MSAFP and fetal infection weak
and thus it cannot be used as a reliable marker of fetal
parvovirus B19 infection (36).
Management of fetal hydrops
Every pregnancy identified with fetal hydrops should be
referred to a tertiary care centre with a maternal-fetal
medicine specialist.
The current management of hydropic fetuses due to
parvovirus B19 infection is somewhat controversial.
The primary management tool is cordocentesis to as-
sess fetal hemoglobin and reticulocyte count. If neces-
sary intrauterine transfusion must be performed (11). If
the fetus is term or near term, delivery should be con-
sidered (11). If delivery is not imminently required, am-
niocentesis for lung maturity evaluation may be consid-
ered. Use of corticosteroids to accelerate lung maturity
Journal of Prenatal Medicine 2010; 4 (4): 63-66
is not controindicated. For fetuses at younger gesta-
tional ages or with pulmonary immaturity, the manage-
ment options of expectant management or intravascu-
lar transfusion (11, 21) have been proposed. There are
no randomized trials to evaluate the best management
for fetal hydrops caused by parvovirus B19 infection.
The upper limit of gestational age for transfusion is
case and centre dependent. Due to myocarditis, the de-
gree of hydrops may not correlate with fetal hemoglo-
bin. Preliminary information has suggested a role for
Doppler assessment of umbilical venous and middle
cerebral artery flow velocities in the assessment of fetal
anemia (37-40). A summary of case reports of intravas-
cular transfusion for fetal hydrops due to parvovirus
B19 infection revealed a fetal mortality rate of 11%. In
all 18 cases, the fetal hemoglobin was less than 8 g/dL,
and most had severe hydrops. Twenty cases were
treated expectantly, with serial ultrasounds noting a fe-
tal mortality of 26%. In those cases managed expec-
tantly, this management was chosen based on the fact
that the hydrops appeared to be mild or improving
(based on ultrasound and/or cordocentesis). Failey et
al. (41) compared outcomes of expectant management
with intravascular transfusion, controlling for severity of
hydrops and gestational age, and found a greater than
7-fold reduction in fetal death with intravascular transfu-
sion. In a survey of maternal-fetal medicine specialists
involving 539 cases of parvovirus B19-induced hy-
drops, death occurred after intravascular transfusion in
6% of cases, and in 30% of cases without intravascular
transfusion (30).
Conclusion
Most women with B19 infection in pregnancy had a sat-
isfactory outcome, but there is nevertheless a substan-
tial risk of fetal loss and non immune hydrops in the sec-
ond trimester. An early diagnosis of fetal anemia due to
parvovirus infection is possible. If a maternal infection is
suspicted the woman should be referred to a terziary
center of fetal maternal medicine.
Bibliografia
11. Feldman DM, Timms D, Borgida AF. Toxoplasmosis,
parvovirus, and cytomegalovirus in pregnancy. Clin
Lab Med. 2010 Sep;30(3):709-20.
12. Crane J. Parvovirus B19 infection in pregnancy. J
Obstet Gynaecol Can. 2002 Sep;24(9):727-43.
13. Tolfvenstam T, Broliden K. Parvovirus B19 infection.
Semin Fetal Neonatal Med. 2009 Aug;14(4):218-21
14. Ergaz Z, Ornoy A. Parvovirus B19 in pregnancy Re-
prod Toxicol. 2006 May;21(4):421-35.
15. de Haan TR, de Jong EP, Oepkes D, Vandenbuss-
che FP, Kroes AC, Walther FJ. Infection with human
parvovirus B19 (‘fifth disease’) during pregnancy:
potential life-threatening implications for the foetus.
Ned Tijdschr Geneeskd. 2008 May 24;152(21):
1185-90.
16. Public Health Laboratory Service Working Party on
Fifth Disease. Prospective study of human parvovirus
infection in pregnancy. Br Med J 1990;300:1166–70.
17. Miller E, Fairley CK, Cohen BJ, Seng C. Immediate
65
E. Giorgio et al.
and long-term outcome of human parvovirus B19 in-
fection in pregnancy. Br J Obstet Gynaecol
1998;105:174–8.
18. Rodis JF, Quinn DL, Gary GW Jr, Anderson LJ,
Rosengren S, Cartter M, et al. Management and out-
comes of pregnancies complicated by human B19
parvovirus infection: a prospective study. Am J Ob-
stet Gynecol 1990;163: 1168–71.
19. Cohen B. Parvovirus B19: an expanding spectrum of
disease. Br Med J 1995;311:1549–52.
10. Levy R ,Weissman A, Blomberg G, Hagay ZJ. Infec-
tion by parvovirus B19 during pregnancy: a review.
Obstet Gynecol Survey 1997;52:254–9.
11. Markenson GR, Yancey MK. Parvovirus B19 infec-
tion in pregnancy. Seminars Perinatol
1998;22:309–17.
12. Centers for Disease Control. Risks associated with
human parvovirus B19 infection. MMWR Morb Mor-
tal Wkly Rep 1989; 38:81–97.
13. Harger JH, Alder SP,Koch WC, Harger GF. Prospec-
tive evaluation of 618 pregnant women exposed to
parvovirus B19: risks and symptoms. Obstet Gynecol
1998;91:413–20.
14 Gratacos E, Torres PJ, Vidal J, Antolin E, Costa J, Ji-
menez de Anta MT, et al. The incidence of human
parvovirus B19 infection during pregnancy and its
impact on perinatal outcome. J Infect Dis
1995;171:1360–3.
15. Guidozzi F, Ballot D, Rothberg A. Human B19 par-
vovirus infection in an obstetric population – a
prospective study determining fetal outcome. J Re-
prod Med. 1994 Jan;39(1):36-8
16. Rodis JF, Rodner C, Hansen AA, Borgida AF, Deo-
liveira I, Rosengren SS. Long-term outcome of chil-
dren following maternal human parvovirus B19 in-
fection. Obstet Gynecol 1998;91:125–8.
17. de Jong EP, de Haan TR, Kroes AC, Beersma MF,
Oepkes D, Walther FJ. Parvovirus B19 infection in
pregnancy. J Clin Virol. 2006 May;36(1):1-7
18. Tolfvenstam T, Broliden K Parvovirus B19 infection.
Semin Fetal Neonatal Med. 2009 Aug;14(4):218-21
19. Morita E, Nakashima A, Asao H, Sato H, Sugamura
K. Human parvovirus B19 nonstructural protein
(NS1) induces cell cycle arrest at G(1) phase. J Vi-
rol. 2003 Mar;77(5):2915-21.
20. Torok T. Human parvovirus B19. In: Remington JS,
Klein JO, editors. Infectious disease of the fetus and
newborn infant. 4th ed. Philadelphia: Saunders;
1995. p. 668–702.
21. Rodis JF. Parvovirus infection. Clin Obstet Gynecol
1999;42:107–20.
22. Saint-Martin J, Choulot JJ, Bonnaud E, Morinet F.
Myocarditis caused by parvovirus. J Pediatr
1990;116:1007–8.
23. Koch WC, Adler SP, Harger J. Intrauterine par-
vovirus B19 infection may cause an asymptomatic
or recurrent postnatal infection. Ped Infect Dis J
1993:12:747–50.
24. Metzman R, Anand A, DeGiulio A, Knisely AS. He-
patic disease associated with intrauterine parvovirus
B19 infection in a newborn premature infant. J Pedri-
atr Gastroenterol Nutr 1989;9:112–4.
66
25. Yoto Y,Kudoh T, Asanuma H, Numazaki K,Tsutsumi
Y, Nakata S, et al. Transient disturbance of con-
sciousness and hepatic dysfunction with human par-
vovirus B19 infection. Lancet 1994;344:624–5.
26. Porter HJ, Quantrill AM, Fleming KA. B19 parvovirus
infection of myocardial cells. Lancet 1988;1:535–6.
27. Ryan G,Kelly EN, Inwood S, et al. Longterm pedi-
atric follow up in nonimmune hydrops secondary to
parvovirus infection. Am J Obstet Gynecol 1997:
176(Part 2): S86.
28. Crane JMG. Prenatal exposure to viral infections.
Can J CME 1998;10:61–74.
29. Gillespie SM, Cartter ML, Asch S, Rokos JB, Gary
GW,Tsou CJ, et al. Occupational risk of human par-
vovirus B19 infection for school and day-care per-
sonnel during an outbreak of erythema infectiosum.
J Am Med Assoc 1990;263: 2061–5.
30. Rodis JF, Borgida AF, Wilson M, Egan JF, Leo MV,
Oibo AO, et al. Management of parvovirus infection
in pregnancy and outcomes of hydrops: a survey of
members of the Society of Perinatal Obstetricians.
Am J Obstet Gynecol 1998;179:985–8
31. Barrett J, Ryan G, Morrow R, Farine D,Kelly E, Ma-
hony J. Human parvovirus B19 during pregnancy. J
Soc Obstet Gynaecol Can 1994;16:1253–8.
32. Rodis JF,Hovick TJ Jr, Quinn DL, Rosengren
SS,Tattersall P. Human parvovirus infection in preg-
nancy. Obstet Gynecol 1988;72:733–8.
33. Pryde PG, Nugent CE, Pridjian G, Barr M, Faix RG.
Spontaneous resolution of nonimmune hydrops fe-
talis secondary to human parvovirus B19 infection.
Obstet Gynecol 1992;79:859–61.
34. Carrington D, Gilmore DH,Whittle MJ, Aitken D, Gib-
son AA, Patrick WJ, et al. Maternal serum α-fetopro-
tein - a marker of fetal aplastic crisis during intrauter-
ine human parvovirus infection. Lancet 1987;1: 433-5.
35. Bernstein IM, Capeless EL. Elevated maternal
serum alpha-fetoprotein and hydrops fetalis in asso-
ciation with fetal parvovirus B19 infection. Obstet
Gynecol 1989;74:456–7.
36. Johnson DR, Fisher RA, Helwick JJ, Murray DL,
Patterson MJ, Downes FP. Screening maternal
serum alpha-fetoprotein levels and human par-
vovirus antibodies. Prenat Diag 1994;14:455–8.
37. Mari G. Noninvasive diagnosis by Doppler ultra-
sonography of fetal anemia due to maternal red-cell
alloimmunization. N Engl J Med 2000:342:9–14.
38. Roberts AB, Mitchell JM, Lake Y, Pattison NS. Ultra-
sonographic surveillance in red blood cell alloimmu-
nization. Am J Obstet Gynecol 2001;184:1251–5.
39. Divakaran TG, Waugh J, Clark TJ, Khan KS, Whittle
MJ, Kilby MD. Noninvasive techniques to detect fe-
tal anemia due to red blood cell alloimmunization: a
systematic review. Obstet Gynecol 2001;98:509–17.
40. Oepkes D. Invasive versus non-invasive testing in
red-cell alloimmunized pregnancies. Eur J Obstet
Gynecol Reprod 2000;92:83–9.
41. Fairley CK, Smoleniec JS, Caul OE, Miller E. Obser-
vational study of effect of intrauterine transfusion on
outcome of fetal hydrops after parvovirus B19 infec-
tion. Lancet 1995;346:1335–7.
Journal of Prenatal Medicine 2010; 4 (4): 63-66